Mammalian protein found in Homo sapiens
SLC22A12 |
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Identifiers |
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Aliases | SLC22A12, solute carrier family 22 (organic anion/urate transporter), member 12, OAT4L, RST, URAT1, solute carrier family 22 member 12 |
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External IDs | OMIM: 607096 MGI: 1195269 HomoloGene: 56442 GeneCards: SLC22A12 |
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Gene location (Human) |
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| Chr. | Chromosome 11 (human)[1] |
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| Band | 11q13.1 | Start | 64,590,641 bp[1] |
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End | 64,602,353 bp[1] |
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Gene location (Mouse) |
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| Chr. | Chromosome 19 (mouse)[2] |
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| Band | 19|19 A | Start | 6,585,875 bp[2] |
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End | 6,593,062 bp[2] |
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RNA expression pattern |
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Bgee | Human | Mouse (ortholog) |
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Top expressed in | - kidney
- renal cortex
- renal medulla
- mammary gland
- breast
- adipose tissue
- liver
- subcutaneous adipose tissue
- rhombencephalon
- abdominal wall
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| Top expressed in | - kidney
- renal cortex
- proximal tubule
- outer renal medulla
- proximal convoluted tubule
- proximal straight tubule
- distal tubule
- hypothalamus
- spinal ganglia
- bone marrow
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| More reference expression data |
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BioGPS | |
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Gene ontology |
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Molecular function | - sodium-independent organic anion transmembrane transporter activity
- PDZ domain binding
- inorganic anion exchanger activity
- urate transmembrane transporter activity
- transmembrane transporter activity
| Cellular component | - integral component of plasma membrane
- extracellular exosome
- apical plasma membrane
- membrane
- plasma membrane
- integral component of membrane
- brush border membrane
| Biological process | - sodium-independent organic anion transport
- urate transport
- cellular homeostasis
- ion transport
- urate metabolic process
- transmembrane transport
- organic acid transmembrane transport
- inorganic anion transport
- transport
- organic anion transport
| Sources:Amigo / QuickGO |
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Orthologs |
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Species | Human | Mouse |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNA) | |
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NM_001276326 NM_001276327 NM_144585 NM_153378 |
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RefSeq (protein) | |
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NP_001263255 NP_001263256 NP_653186 NP_700357 |
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Location (UCSC) | Chr 11: 64.59 – 64.6 Mb | Chr 19: 6.59 – 6.59 Mb |
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PubMed search | [3] | [4] |
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Wikidata |
View/Edit Human | View/Edit Mouse |
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Solute carrier family 22 (organic anion/cation transporter), member 12, also known as SLC22A12 and URAT1, is a protein which in humans is encoded by the SLC22A12 gene.[5][6]
Function
The protein encoded by this gene is a urate transporter and urate-anion exchanger which regulates the level of urate in the blood. This protein is an integral membrane protein primarily found in kidney. Two transcript variants encoding different isoforms have been found for this gene.[5]
Clinical significance
Numerous single nucleotide polymorphisms of this gene are significantly associated with altered (increased or decreased) reabsorption of uric acid by the kidneys.[7][8] Respectively, these altered rates of reabsorption contribute to hyperuricemia and hypouricemia.
Interactions
SLC22A12 has been shown to have a protein-protein interaction with PDZK1.[9]
Inhibition
Lesinurad,Ruzinurad and dotinurad are urate transporter inhibitors that have been approved to treat gout.[10][11] Lesinurad enhances urate excretion by inhibition the tubular re-absorption. Probenecid also facilitates uric acid secretion.[12][13]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000197891 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000061742 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: SLC22A12 solute carrier family 22 (organic anion/cation transporter), member 12".
- ^ Enomoto A, Kimura H, Chairoungdua A, Shigeta Y, Jutabha P, Cha SH, Hosoyamada M, Takeda M, Sekine T, Igarashi T, Matsuo H, Kikuchi Y, Oda T, Ichida K, Hosoya T, Shimokata K, Niwa T, Kanai Y, Endou H (May 2002). "Molecular identification of a renal urate anion exchanger that regulates blood urate levels". Nature. 417 (6887): 447–52. Bibcode:2002Natur.417..447E. doi:10.1038/nature742. PMID 12024214. S2CID 4417844.
- ^ Graessler J, Graessler A, Unger S, Kopprasch S, Tausche AK, Kuhlisch E, Schroeder HE (January 2006). "Association of the human urate transporter 1 with reduced renal uric acid excretion and hyperuricemia in a German Caucasian population". Arthritis Rheum. 54 (1): 292–300. doi:10.1002/art.21499. PMID 16385546.
- ^ Wakida N, Tuyen DG, Adachi M, Miyoshi T, Nonoguchi H, Oka T, Ueda O, Tazawa M, Kurihara S, Yoneta Y, Shimada H, Oda T, Kikuchi Y, Matsuo H, Hosoyamada M, Endou H, Otagiri M, Tomita K, Kitamura K (April 2005). "Mutations in human urate transporter 1 gene in presecretory reabsorption defect type of familial renal hypouricemia". J. Clin. Endocrinol. Metab. 90 (4): 2169–74. doi:10.1210/jc.2004-1111. PMID 15634722.
- ^ Gisler SM, Pribanic S, Bacic D, Forrer P, Gantenbein A, Sabourin LA, Tsuji A, Zhao ZS, Manser E, Biber J, Murer H (November 2003). "PDZK1: I. a major scaffolder in brush borders of proximal tubular cells". Kidney Int. 64 (5): 1733–45. doi:10.1046/j.1523-1755.2003.00266.x. PMID 14531806.
- ^ "FDA approves Zurampic to treat high blood uric acid levels associated with gout". United States Food and Drug Administration. 22 December 2015.
- ^ "List of Approved Products" (PDF). Pharmaceuticals and Medical Devices Agency.
- ^ Hsyu PH, Gisclon LG, Hui AC, Giacomini KM (January 1988). "Interactions of organic anions with the organic cation transporter in renal BBMV". The American Journal of Physiology. 254 (1 Pt 2): F56–61. doi:10.1152/ajprenal.1988.254.1.F56. PMID 2962517.
- ^ Silverman W, Locovei S, Dahl G (September 2008). "Probenecid, a gout remedy, inhibits pannexin 1 channels". American Journal of Physiology. Cell Physiology. 295 (3): C761–7. doi:10.1152/ajpcell.00227.2008. PMC 2544448. PMID 18596212.
Further reading
- Hediger MA, Johnson RJ, Miyazaki H, Endou H (2005). "Molecular physiology of urate transport". Physiology. 20 (2): 125–33. doi:10.1152/physiol.00039.2004. PMID 15772301.
- Enomoto A, Kimura H, Chairoungdua A, Shigeta Y, Jutabha P, Cha SH, Hosoyamada M, Takeda M, Sekine T, Igarashi T, Matsuo H, Kikuchi Y, Oda T, Ichida K, Hosoya T, Shimokata K, Niwa T, Kanai Y, Endou H (2002). "Molecular identification of a renal urate anion exchanger that regulates blood urate levels". Nature. 417 (6887): 447–52. Bibcode:2002Natur.417..447E. doi:10.1038/nature742. PMID 12024214. S2CID 4417844.
- Gisler SM, Pribanic S, Bacic D, Forrer P, Gantenbein A, Sabourin LA, Tsuji A, Zhao ZS, Manser E, Biber J, Murer H (2004). "PDZK1: I. a major scaffolder in brush borders of proximal tubular cells". Kidney Int. 64 (5): 1733–45. doi:10.1046/j.1523-1755.2003.00266.x. PMID 14531806.
- Ichida K, Hosoyamada M, Hisatome I, Enomoto A, Hikita M, Endou H, Hosoya T (2004). "Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion". J. Am. Soc. Nephrol. 15 (1): 164–73. doi:10.1097/01.ASN.0000105320.04395.D0. PMID 14694169.
- Anzai N, Miyazaki H, Noshiro R, Khamdang S, Chairoungdua A, Shin HJ, Enomoto A, Sakamoto S, Hirata T, Tomita K, Kanai Y, Endou H (2004). "The multivalent PDZ domain-containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus". J. Biol. Chem. 279 (44): 45942–50. doi:10.1074/jbc.M406724200. PMID 15304510.
- Iwai N, Mino Y, Hosoyamada M, Tago N, Kokubo Y, Endou H (2004). "A high prevalence of renal hypouricemia caused by inactive SLC22A12 in Japanese". Kidney Int. 66 (3): 935–44. doi:10.1111/j.1523-1755.2004.00839.x. PMID 15327384.
- Takahashi T, Tsuchida S, Oyamada T, Ohno T, Miyashita M, Saito S, Komatsu K, Takashina K, Takada G (2005). "Recurrent URAT1 gene mutations and prevalence of renal hypouricemia in Japanese". Pediatr. Nephrol. 20 (5): 576–8. doi:10.1007/s00467-005-1830-z. PMID 15772829. S2CID 12711324.
- Taniguchi A, Urano W, Yamanaka M, Yamanaka H, Hosoyamada M, Endou H, Kamatani N (2005). "A common mutation in an organic anion transporter gene, SLC22A12, is a suppressing factor for the development of gout". Arthritis Rheum. 52 (8): 2576–7. doi:10.1002/art.21242. PMID 16059895.
- Shima Y, Teruya K, Ohta H (2006). "Association between intronic SNP in urate-anion exchanger gene, SLC22A12, and serum uric acid levels in Japanese". Life Sci. 79 (23): 2234–7. doi:10.1016/j.lfs.2006.07.030. PMID 16920156.
- Ohtsuka Y, Zaitsu M, Ichida K, Isomura N, Tsuji K, Sato T, Hamasaki Y (2007). "Human uric acid transporter 1 gene analysis in familial renal hypo-uricemia associated with exercise-induced acute renal failure". Pediatrics International. 49 (2): 235–7. doi:10.1111/j.1442-200X.2007.02337.x. PMID 17445045. S2CID 25818777.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
By group |
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SLC1–10 |
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(1): | |
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(2): | |
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(3): | |
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(4): | |
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(5): | |
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(6): | |
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(7): | |
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(8): | |
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(9): | |
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(10): | |
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| SLC11–20 |
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(11): | - proton coupled metal ion transporter
|
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(12): | |
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(13): | - human Na+-sulfate/carboxylate cotransporter
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(14): | |
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(15): | - proton oligopeptide cotransporter
|
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(16): | - monocarboxylate transporter
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(17): | |
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(18): | |
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(19): | |
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(20): | - type III Na+-phosphate cotransporter
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| SLC21–30 |
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(21): | |
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(22): | |
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(23): | - Na+-dependent ascorbic acid transporter
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(24): | |
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(25): | |
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(26): | - multifunctional anion exchanger
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(27): | |
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(28): | - Na+-coupled nucleoside transport (SLC28A1
|
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(29): | - facilitative nucleoside transporter
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(30): | |
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| SLC31–40 |
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(31): | |
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(32): | |
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(33): | |
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(34): | - type II Na+-phosphate cotransporter
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(35): | - nucleoside-sugar transporter
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-
-
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- SLC35E1
- SLC35E2
- SLC35E3
- SLC35E4
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(36): | - proton-coupled amino-acid transporter
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(37): | - sugar-phosphate/phosphate exchanger
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(38): | - System A & N, sodium-coupled neutral amino-acid transporter
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(39): | |
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(40): | - basolateral iron transporter
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| SLC41–48 |
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(41): | |
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(42): | |
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(43): | - Na+-independent, system-L like amino-acid transporter
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(44): | |
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(45): | - Putative sugar transporter
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(46): | |
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(47): | |
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(48): | |
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see also solute carrier disorders |
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